Overview
To elucidate mechanisms of substance use disorders (SUD) and comorbid mental illnesses in people living with HIV (PLWH), the investigators propose to investigate reward and pain circuitry in cannabis use and depression comorbidity, two highly prevalent conditions in PLWH. The study will take place in our health system in The Bronx-a persistent epicenter of the HIV epidemic due to profound poverty and health disparities. The focus is on young adults (ages 18-34) to minimize HIV chronicity effects and due to the high rates of SUD and reduced adherence to HIV treatments in this age group; among >31,000 diagnosed young PLWH in The Bronx in 2019, less than 70% had suppressed (<200 copies/mL) viral load (VL).
Description
We propose to investigate reward and pain circuitry in cannabis use and depression comorbidity, two highly prevalent conditions in PLWH. We will focus on young adults (ages 18-34) to minimize HIV neuronal chronicity effects and in light of the high rates of substance use and reduced adherence to HIV treatment in this age group. Our proposed model is: 1) Both reward dysfunction (deficits in reward learning, expectancy, attainment, positive prediction errors) and pain hypersensitivity (pain sensitivity, aversion, negative prediction errors) contribute to cannabis use and depression comorbidity in young PLWH. 2) The habenula (Hb), a small limbic hub, plays a pivotal regulatory role in these processes by inhibiting ventral tegmental area (VTA) reward signals to the nucleus accumbens (NAc) following pain and loss. 3) THC, a major component of cannabis, exerts its psychoactive analgesic effects by binding to cannabinoid 1 receptors in the reward and pain systems, including the anterior cingulate (ACC), periaqueductal gray (PAG), thalamus, amygdala, VTA, NAc, and Hb, creating temporary relief of mood and pain symptoms but resulting in long-term alterations in reward circuitry that exacerbate depression and substance use. 4) Capitalizing on improvements in fMRI resolution, our novel imaging methods overcome prior technical constraints to study the Hb and other small structures critical to reward and pain processing.We will test the overall hypothesis that cannabis use and depression in young PLWH have an additive effect, inducing both reward deficits and pain hypersensitivity, and that this pattern will predict worse outcomes at 1 year follow-up. Investigators will utilize a 2×2 factorial design: 1) 70 depressed cannabis users; 2) 70 depressed cannabis non-users; 3) 70 non-depressed cannabis users; and 4) 70 non-depressed cannabis non-users. To capture a wide range of illness severity, investigators will include subthreshold depression and cannabis use on ≥20 days of the past 30 days. Comprehensive clinical evaluations, a computerized reward task, and blood tests for CD4+ count, VL, and serum THC will be performed at baseline, 6- and 12 months. fMRI (resting-state, RFT, RPET, pain task) and cognitive tests will be done at baseline.
Eligibility
Inclusion Criteria:
- HIV seropositivity confirmed with lab report, medical records, or HIV testing.
- Between the ages of 18-34 years
- Fluency in English or Spanish
- Ability to provide informed consent and perform study procedures, including estimated full-scale IQ >75 to ensure that participants are able to understand the study.
- Cannabis users: To capture a wide range of cannabis use frequency, meeting DSM-5 criteria for CUD will not be required. However, in order to ensure sufficient exposure, cannabis use will be significant (self-reported use on ≥20 of the prior 30 days and positive THC urine toxicology).
- Depressed: In order to capture a wide range of depression illness severity, we will allow participants with subthreshold depression, defined as a raw severity score of ≥12 on the Montgomery Asberg Depression Rating Scale (MADRS).
Exclusion Criteria:
- Perinatally acquired HIV infection, as early neurodevelopmental alterations and HIV legacy effects may exist in this group
- Pregnancy or lactation
- Current Substance Use Disorder other than cannabis or nicotine
- Certified for or self-reported medical cannabis use, or intent to become certified
- Current cocaine use by self-report or urine toxicology
- CNS disease or injury, or neuro-degenerative disease
- Unique pain syndromes (e.g. multiple sclerosis, rheumatoid arthritis);
- Severe medical illness such as end-stage renal disease, heart failure, cirrhosis, or cancer
- MRI contraindication such as claustrophobia, metallic ink tattoos, or pacemaker.
Depressed cannabis non-users:
- At baseline, all participants will be psychotropic-medication-free for ≥1 month prior to study enrollment (or ≥3 months for medications with longer half-lives). Benzodiazepines and sleeping aids taken on an as-needed basis will be allowed, however we will require a 4-day abstinence period before the scan.
- Exclusionary are participants with a DSM-5 diagnoses of bipolar disorder, psychotic disorders, autism spectrum disorders, and all non-cannabis substance-related disorders will be exclusionary. disorder (PTSD) are not uncommon among depressed individuals and will be
- Anxiety disorders, obsessive-compulsive disorder (OCD), and post-traumatic stress are allowed as long as depressive symptoms are primary.
atypical of depression. • Suicidal ideations (SI) without a specific plan (defined as
passive SI) are common in depression and will be allowed. However, if SI constitutes an
imminent risk to self or others (defined as active SI), the participant will be withdrawn
from the study and emergency procedures will be initiated immediately, including ER
admission.
Depressed cannabis users:
• Exclusion criteria will be the same as depressed cannabis non-users except for cannabis
use.
Non-depressed cannabis users:
• Will have no major psychiatric conditions other than cannabis use/disorder.
Non-depressed cannabis non-users:
• Exclusion criteria will be the same as for non-depressed cannabis users; in addition
participants will not report cannabis use in the prior 90 days and have a urine toxicology
test negative for cannabis.